Inhibition of Akt signaling by SN-38 induces apoptosis in cervical cancer.
Cervical cancer still remains a major health problem in women worldwide. Inhibitors of topoisomerase I have proven to be among the most promising new classes of anti-neoplastic agents introducing into the clinic in recent years. CPT-11 is one of the most widely used Camptothecin analogues and is converted to form the active metabolite SN-38. The study tried to explore the in vitro mechanisms of apoptosis induced by SN-38 in cervical cancer cell lines HeLa and SiHa. The results demonstrated here that SN-38 inhibited cell proliferation in a time- and dose-dependant manner. Western Blot showed that SN-38 down-regulated protein expression of p-Akt and increased protein expression of p53 and p21, but it had no effects on protein expression of Bax, Bcl-2 and Akt. Transfection of the full-length Akt cDNA into HeLa and SiHa cells resulted in the reduction of apoptosis induced by SN-38, and Akt kinase activity regulated the p53 pathway, indicating that inhibition of the Akt pathway played an important role in exhibition of SN-38-mediated cytotoxic effect. Our data suggested that SN-38 could induce apoptosis through a p53 pathway and that activation of p53 in response to S-38 is governed by Akt.
Liu
Youqing
Y
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
Xing
Hui
H
Weng
Danhui
D
Song
Xiaohong
X
Qin
Xiaomin
X
Xia
Xi
X
Weng
Yanjie
Y
Liang
Fengqi
F
Chen
Gang
G
Han
Xiaobing
X
Ma
Xiaoli
X
Wang
Shixuan
S
Zhou
Jianfeng
J
Xu
Gang
G
Meng
Li
L
Ma
Ding
D
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000077146:Irinotecan; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
D000972:Antineoplastic Agents, Phytogenic; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000077146:Irinotecan; D051057:Proto-Oncogene Proteins c-akt; D002166:Camptothecin